Synthesis of the 5'-C-phosphonate of 4(S)-(6-amino-9H-purin-9-yl) tetrahydro-2(S)-furanmethanol [S,S-IsoddA]

Nair, Vasu; Sharma, Pawan K.

doi:10.3998/ark.5550190.0004.f02

Cited by 7 publications

(8 citation statements)

References 9 publications

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“…The lack of cytotoxicity of the tested molecules to either cancer or non-malignant cells reflects the lower propensity of terminal nucleosides than non-terminal ones to exhibit cytotoxic effects. It is known that 2′-isonucleosides can be, although in a low extend, intracellularly phosphorylated at the primary hydroxyl group by kinases [9,23] and that isonucleoside triphosphates can be recognized by DNA polymerases and be incorporated into the growing DNA chain arresting its elongation [24], similarly to the mechanism of action of the known anticancer nucleosides [1,2]. The absence of a terminal hydroxyl group able for phosphorylation in these newly synthesized 5′-/6′-isonucleosides precludes them to undergo such biological pathway which eventually would lead to cytotoxic effects.…”

Section: Discussionmentioning

confidence: 99%

Synthesis and Biological Evaluation of Structurally Varied 5′-/6′-Isonucleosides and Theobromine-Containing N-Isonucleosidyl Derivatives

et al. 2019

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Isonucleosides are rather stable regioisomeric analogs of nucleosides with broad therapeutic potential. We have previously demonstrated the ability of 5′ and 6′-isonucleosides to inhibit the activity of acetylcholinesterase, a major target for Alzheimer’s disease therapy. Continuing with our research on this topic, we report herein on the synthesis and biological evaluation of a variety of novel terminal isonucleosides and theobromine isonucleotide analogs. Xylofuranose-based purine or uracil 5′-isonucleosides and xylofuranos-5′-yl or glucos-6′-yl theobromine derivatives were accessed via Mitsunobu coupling between partially protected xylofuranose or glucofuranose derivatives with a nucleobase using conventional or microwave-assisted heating conditions. Theobromine-containing N-isonucleosidyl sulfonamide and phosphoramidate derivatives were synthesized from isonucleosidyl acetate precursors. The most active compounds in the cholinesterase inhibition assays were a glucopyranose-based theobromine isonucleosidyl acetate, acting as a dual inhibitor of acetylcholinesterase (AChE, Ki = 3.1 µM) and butyrylcholinesterase (BChE, Ki = 5.4 µM), and a 2-O,4-O-bis-xylofuranos-5′-yl uracil derivative, which displayed moderate inhibition of AChE (Ki = 17.5 µM). Docking studies revealed that the active molecules are positioned at the gorge entrance and at the active site of AChE. None of the compounds revealed cytoxic activity to cancer cells as well as to non-malignant mouse fibroblasts.

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Section: Discussionmentioning

confidence: 99%

Synthesis and Biological Evaluation of Structurally Varied 5′-/6′-Isonucleosides and Theobromine-Containing N-Isonucleosidyl Derivatives

et al. 2019

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“…Phosphonate 120 shows a much lower activity compared to the parent compound ( S , S )-isoddA . Derivatives 121a – d do not show antiviral activity in vitro .…”

Section: Biological Activity Of Nucleobase- or 4′-hydroxymethyl-trans...mentioning

confidence: 96%

“…131 Phosphonate 120 shows a much lower activity compared to the parent compound (S,S)-isoddA. 132 Derivatives 121a−d do not show antiviral activity in vitro. 133 Compounds 122a−c and 123a−c were found inactive against HCMV, 126 but the carbocyclic guanine phosphonate 124 shows reasonable activity against HIV in CEM cells (IC 50 = 20 μM).…”

Section: Isonucleoside Phosphonatesmentioning

confidence: 99%

“…The 5′-phosphonate analogue of (S,S)-isoddA (120) was synthesized by Nair and Sharma through direct Mitsunobu insertion of adenine into a phosphono pseudosugar obtained in an Arbuzov reaction from the corresponding 5-iodofuranose and triethyl phosphite. 132 Additionally, 2′-O-phosphonomethyl base-transposed nucleosides 122 and 123 together with carbocyclic guanine analogue 124 were readily obtained through the ring opening of 3,4-epoxytetrahydrofuran 126 or 1,2-epoxycyclopentane, 134 respectively. An interesting contri- bution includes the preparation of unusual isomeric nucleosides 121 with a phosphono group directly connected at the C-1′ of the furanose ring (Scheme 34).…”

Section: Hydroxymethyl-deleted and Base-transposed Nucleoside Phospho...mentioning

confidence: 99%

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Nucleosides with Transposed Base or 4′-Hydroxymethyl Moieties and Their Corresponding Oligonucleotides

et al. 2015

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This review focuses on 4'-hydroxymethyl- or nucleobase-transposed nucleosides, nucleotides, and nucleoside phosphonates, their stereoisomers, and their close analogues. The biological activities of all known 4'-hydroxymethyl- or nucleobase-transposed nucleosides, nucleotides, and nucleoside phosphonates as potential antiviral or anticancer agents are compiled. The routes that have been taken for the chemical synthesis of such nucleoside derivatives are described, with special attention to the innovative strategies. The enzymatic synthesis, base-pairing properties, structure, and stability of oligonucleotides containing nucleobase- or 4'-hydroxymethyl-transposed nucleotides are discussed. The use of oligonucleotides containing nucleobase- or 4'-hydroxymethyl-transposed nucleotides as small oligonucleotide (e.g., human immunodeficiency virus integrase) inhibitors, in applications such as antisense therapy, silencing RNA (siRNA), or aptamer selections, is detailed.

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“…Architectural analyses and excavations in the Cuzco area have largely concentrated on these later monumental Inka complexes and elite spaces (Alcina Franch 1976; Bengsston 1998;Burger and Salazar, eds. 2004;Farrington and Zapata 2003;Gibaja Oviedo 1982Nair 2003;Niles 1999;Paredes 2003;Protzen 1993Protzen , 2000Valcárcel 1934Valcárcel , 1935Valencia Zegarra and Gibaja Oviedo 1992; see also Bauer 2004).…”

Section: Read Only/no Downloadmentioning

confidence: 99%

The Construction of Value in the Ancient World

Voutsaki¹

2012

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The CoTsen InsTITuTe of ArChAeology Press is the publishing unit of the Cotsen Institute of Archaeology at UCLA. The Cotsen Institute is a premier research organization dedicated to the creation, dissemination, and conservation of archaeological knowledge and heritage. It is home to both the Interdepartmental Archaeology Graduate Program and the UCLA/Getty Master's Program in the Conservation of Archaeological and Ethnographic Materials. The Cotsen Institute provides a forum for innovative faculty research, graduate education, and public programs at UCLA in an effort to impact positively the academic, local and global communities. Established in 1973, the Cotsen Institute is at the forefront of archaeological research, education, conservation and publication and is an active contributor to interdisciplinary research at UCLA. The Cotsen Institute Press specializes in producing high-quality academic volumes in several different series, including Monographs, World Heritage and Monuments, Cotsen Advanced Seminars, and Ideas, Debates and Perspectives. The Press is committed to making the fruits of archaeological research accessible to professionals, scholars, students, and the general public. We are able to do this through the generosity of Lloyd E. Cotsen, longtime Institute volunteer and benefactor, who has provided an endowment that allows us to subsidize our publishing program and produce superb volumes at an affordable price. Publishing in nine different series, our awardwinning archaeological publications receive critical acclaim in both the academic and popular communities.

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Synthesis of the 5'-C-phosphonate of 4(S)-(6-amino-9H-purin-9-yl) tetrahydro-2(S)-furanmethanol [S,S-IsoddA]

Cited by 7 publications

References 9 publications

Synthesis and Biological Evaluation of Structurally Varied 5′-/6′-Isonucleosides and Theobromine-Containing N-Isonucleosidyl Derivatives

Synthesis and Biological Evaluation of Structurally Varied 5′-/6′-Isonucleosides and Theobromine-Containing N-Isonucleosidyl Derivatives

Nucleosides with Transposed Base or 4′-Hydroxymethyl Moieties and Their Corresponding Oligonucleotides

The Construction of Value in the Ancient World

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